Gen. Code and Des.
66078 collagenase Clostridium hist. INJECTION VIAL 0.9 MG
Fine Line Class
850085008510 All Rx Products
1890 collagenase Clostridium histolyticum 9001121
2598 sucrose 57501
SINGLE DOSE VIAL
ZB Particular pharmaceutical entity was not evaluated.
Drug Form Pack Size
Retail Pack Quantity
Special Storage Cond.
30 Refrige./DoNot Freez
XIAFLEX- collagenase clostridium histolyticum
Auxilium Pharmaceuticals, Inc.
WARNING: CORPORAL RUPTURE (PENILE FRACTURE) OR OTHER SERIOUS PENILE INJURY IN THE TREATMENT OF PEYRONIE'S DISEASE
Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) XIAFLEX-treated patients in clinical studies. In other XIAFLEX-treated patients (9 of 1044; 0.9%), a combination of penile ecchymoses or hematoma, sudden penile detumescence, and/or a penile "popping" sound or sensation was reported, and in these cases, a diagnosis of corporal rupture cannot be excluded. Severe penile hematoma was also reported as an adverse reaction in 39 of 1044 (3.7%) XIAFLEX-treated patients [see Warnings and Precautions (5.2)].
Signs or symptoms that may reflect serious penile injury should be promptly evaluated to assess for corporal rupture or severe penile hematoma which may require surgical intervention [see Warnings and Precautions (5.2)].
Because of the risks of corporal rupture or other serious penile injury, XIAFLEX is available for the treatment of Peyronie's disease only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XIAFLEX REMS Program [see Warnings and Precautions (5.3)].
1 INDICATIONS AND USAGE
XIAFLEX is indicated for the treatment of adult patients with Dupuytren's contracture with a palpable cord.
XIAFLEX is indicated for the treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage and Administration for Dupuytren's Contracture
Dosing Overview for Dupuytren's Contracture
XIAFLEX should be administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of patients with Dupuytren's contracture.
XIAFLEX, supplied as a lyophilized powder, must be reconstituted with the provided diluent prior to use [see Dosage and Administration (2.1)]. The dose of XIAFLEX is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint [see Dosage and Administration (2.1)]. Each vial of XIAFLEX and sterile diluent should only be used for a single injection. If two joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection. Table 1 displays an overview of the volumes of sterile diluent for reconstitution and the reconstituted XIAFLEX solution to be used in the intralesional injection [see Dosage and Administration (2.1)]. Approximately 24 to 72 hours after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption
The reconstituted XIAFLEX solution to be used in the intralesional injection contains 0.58 mg of XIAFLEX. Note: The entire reconstituted XIAFLEX solution contains 0.9 mg of XIAFLEX. Reconstituted XIAFLEX solution remaining in the vial after the injection should be discarded.
For cords affectingMP joints For cords affectingPIP joints
Sterile Diluent for Reconstitution
Volume 0.39 mL 0.31 mL
Reconstituted XIAFLEX Solution to be Injected1
Volume 0.25 mL 0.20 mL
Four weeks after the XIAFLEX injection and finger extension procedure, if a MP or PIP contracture remains, the cord may be re-injected with a single dose of 0.58 mg of XIAFLEX and the finger extension procedure may be repeated (approximately 24 to 72 hours after injection). Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.
Perform up to two injections in the same hand according to the injection procedure during a treatment visit. Two palpable cords affecting two joints may be injected or one palpable cord affecting two joints in the same finger may be injected at two locations during a treatment visit. If a patient has other palpable cords with contractures of MP or PIP joints, these cords may be injected with XIAFLEX at other treatment visits approximately 4 weeks apart.
Reconstitution of the Lyophilized Powder for Dupuytren's Contracture
Before use, remove the vial(s) containing the lyophilized powder of XIAFLEX and the vial(s) containing the diluent for reconstitution from the refrigerator and allow the vials to stand at room temperature for at least 15 minutes and no longer than 60 minutes. Visually inspect the vial(s) containing XIAFLEX. The cake of lyophilized powder should be intact and white in color.
After removal of the flip-off cap from each vial, using aseptic technique swab the rubber stopper and surrounding surface of the vial(s) containing XIAFLEX and the vial(s) containing the diluent for reconstitution with sterile alcohol (no other antiseptics should be used).
Use only the supplied diluent for reconstitution. The diluent contains calcium which is required for the activity of XIAFLEX.
Using a 1 mL syringe that contains 0.01 mL graduations with a 27-gauge �-inch needle (not supplied), withdraw a volume of the diluent supplied , as follows:
0.39 mL for cords affecting a MP joint or
0.31 mL for cords affecting a PIP joint.
Inject the diluent slowly into the sides of the vial containing the lyophilized powder of XIAFLEX. Do not invert the vial or shake the solution. Slowly swirl the solution to ensure that all of the lyophilized powder has gone into solution. If administering two injections in the same hand during a treatment visit, use a new syringe to reconstitute a second vial of XIAFLEX with a second vial of diluent.
The reconstituted XIAFLEX solution can be kept at room temperature (20� to 25�C/68� to 77�F) for up to one hour or refrigerated at 2� to 8�C (36� to 46�F) for up to 4 hours prior to administration. If the reconstituted XIAFLEX solution is refrigerated, allow this solution to return to room temperature for approximately 15 minutes before use.
Discard the syringe(s) and needle(s) used for reconstitution and the diluent vial(s).
Dosage and Administration for Peyronie's Disease
Dosing Overview for Peyronie's Disease XIAFLEX should be administered by a healthcare provider experienced in the treatment of male urological diseases, who has completed required training for use of XIAFLEX in the treatment of Peyronie's disease.
XIAFLEX, supplied as a lyophilized powder, must be reconstituted with the provided diluent prior to use [see Dosage and Administration (2.2)]. The dose of XIAFLEX is 0.58 mg per injection administered into a Peyronie's plaque. If more than one plaque is present, inject into the plaque causing the curvature deformity.
A treatment course consists of a maximum of 4 treatment cycles. Each treatment cycle consists of two XIAFLEX injection procedures [see Dosage and Administration (2.2)] and one penile modeling procedure [see Dosage and Administration (2.2)]. The second XIAFLEX injection procedure is performed 1 to 3 days after the first. The penile modeling procedure is performed 1 to 3 days after the second injection of the treatment cycle. The interval between treatment cycles is approximately six weeks. The treatment course therefore, consists of a maximum of 8 injection procedures and 4 modeling procedures.
If the curvature deformity is less than 15 degrees after the first, second or third treatment cycle, or if the healthcare provider determines that further treatment is not clinically indicated, then the subsequent treatment cycles should not be administered.
The safety of more than one treatment course of XIAFLEX is not known.
Table 2 displays an overview of the volume of sterile diluent for reconstitution and the reconstituted XIAFLEX solution to be used in the intralesional injection
DOSAGE FORMS AND STRENGTHS
XIAFLEX is supplied in single-use glass vials containing 0.9 mg of collagenase clostridium histolyticum as a sterile, lyophilized powder for reconstitution. Sterile diluent for reconstitution is provided in the package in a single-use glass vial containing 3 mL of 0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride.
XIAFLEX contains purified collagenase clostridium histolyticum, consisting of two microbial collagenases in a defined mass ratio, Collagenase AUX-I and Collagenase AUX-II, which are isolated and purified from the fermentation of Clostridium histolyticum bacteria.
Collagenase AUX-I is a single polypeptide chain consisting of approximately 1000 amino acids of known sequence. It has an observed molecular weight of 114 kiloDaltons (kDa). It belongs to the class I Clostridium histolyticum collagenases.
Collagenase AUX-II is a single polypeptide chain consisting of approximately 1000 amino acids of deduced sequence. It has an observed molecular weight of 113 kDa. It belongs to the class II Clostridium histolyticum collagenases.
XIAFLEX is supplied as a sterile lyophilized powder (white cake) intended for reconstitution with the supplied sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride) prior to intralesional injection into a Dupuytren's cord or a Peyronie's plaque.
XIAFLEX is available in single-use, glass vials containing 0.9 mg of collagenase clostridium histolyticum. Each vial also contains 0.5 mg of hydrochloric acid, 18.5 mg of sucrose, and 1.1 mg of tromethamine.
12.1 Mechanism of Action
Collagenases are proteinases that hydrolyze collagen in its native triple helical conformation under physiological conditions, resulting in lysis of collagen deposits.
Injection of XIAFLEX into a Dupuytren's cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord.
The signs and symptoms of Peyronie's disease are caused by a collagen plaque. Injection of XIAFLEX into a Peyronie's plaque, which is comprised mostly of collagen, may result in enzymatic disruption of the plaque. Following this disruption of the plaque, penile curvature deformity and patient bother caused by Peyronie's disease are reduced